Zhou et al. BMC Public Health 2014, 14:516 http://www.biomedcentral.com/1471-2458/14/516
RESEARCH ARTICLE
Open Access
Association between hepatitis B virus infection and metabolic syndrome: a retrospective cohort study in Shanghai, China Yanbing Zhou1,2, Yan Cui2, Haiju Deng2 and Jinming Yu3*
Abstract Background: Metabolic syndrome (MS) and hepatitis B (HBV) infection are two major public health problems in China. There are few studies about their association, and the results of these studies are contradictory. We conducted a retrospective cohort study to assess the association between MS and HBV in a Shanghai community-based cohort. Methods: Nine hundred seventy-six Shanghai residents were recruited from the Putuo community. 480 HBV infections were in exposed group and 496 non-infections in unexposed group. All metabolic-related parameters and hepatitis B serology were tested with routine biochemical or immunological methods. “Exposed” was defined by HBV infection represented by hepatitis B surface antigen (HBsAg) and without anti-virus treatment. “Unexposed” were subjects who didn’t infect with HBV (Represented by HBsAg) and no MS when they entered the cohort. MS was defined based on the updated National Cholesterol Education Program Adult Treatment Panel III criteria. The Cox proportional hazards model was used to estimate the hazard ratios (HR) and related 95% confidence intervals (95% CI) for the association between HBV infection and MS over a 20-year follow-up period. Results: Of 976 subjects recruited, 480 had latent HBV infection (exposed subjects). After adjusting for age, the crude HR was 2.46 (95% CI: 1.77, 3.41). After adjusting for potential risk factors of MS (age, gender, smoking, passive smoking, alcohol consumption, physical activity, and diet), the HR was 2.27 (95% CI: 1.52, 3.38). Conclusions: This 20-year follow-up retrospective cohort study in Shanghai showed a positive association between HBV infection and MS.
Background Metabolic syndrome (MS) is a complicated metabolic disorder comprising obesity, hypertension, diabetes, and dyslipidemia. MS has been verified as a risk factor for cardiovascular disease, type 2 diabetes, and renal disease [1-5], and increases mortality from all causes [6]. MS is recognized as a major public health problem worldwide [7,8]. China is endemic for hepatitis B virus (HBV) infection, with a prevalence of nearly 10% [9] in those subjects over 40 in 2006. This age cohort did not receive regular hepatitis B vaccination. Evidence suggests that hepatitis C virus (HCV) infection has an impact on lipid and glucose metabolism [10-14]. A community-based study in Taiwan found HCV infection * Correspondence: [email protected] 3 School of Public Health, Fudan University, Shanghai, P.R. China Full list of author information is available at the end of the article
to be associated with MS (odds ratio 6.4; 95% CI: 1.82 to 22.84) [15]. Similarly to HCV, it is thought that HBV might lead to chronic liver damage by dyslipidemia. A study by Su et al. [16] reported an association between asymptomatic chronic HBV infection and lower serum levels of total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C). This evidence suggests that HBV might affect metabolic profiles and subsequent development of MS. However, studies of the correlation between HBV infection and MS yield contradictory results. Three studies reported a positive association between HBV infection and MS [17-19], two found an inverse association [20,21], and one found no association [22]. The contradictions may be due to small sample size [23] and limitation of subjects to hospital patients [24]. Another study suggested that MS might cause worsening of cirrhosis in chronic HBV patients [25], suggesting a relationship between MS and HBV infection. It is vital to explore the relationship
© 2014 Zhou et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Zhou et al. BMC Public Health 2014, 14:516 http://www.biomedcentral.com/1471-2458/14/516
between two of the major public health problems of China, HBV and MS, to inform prevention and control strategies.
Methods Population and study design
This study was conducted with the approval of the Ethical Review Board in the School of Public Health, Fudan University and conforms to the principles embodied in the Declaration of Helsinki. We evaluated the association between MS and HBV in a community-based retrospective study founded in 1991 in Shanghai. The cohort was from Putuo district, located in the northwest of Shanghai, China. Subjects with HBV were recruited via records from 1991 from the populationbased infectious disease surveillance system. Subjects with latent HBV infections (defined as asymptomatic, but positive for HBV surface antigen for more than 6 months) were classified as “exposed” (Figure 1). After excluding subjects with MS when they entered into the cohort, subjects who had received antiviral or immunosuppressive therapy, and subjects without informed consent, 480 subjects were enrolled into the study. All of them were negative for anti-HCV and other types of hepatitis virus, except for HBV. Four hundred ninety-six subjects negative for HBV surface antigen from the same community were classified
Figure 1 Selection of subjects during study.
Page 2 of 6
as “unexposed”. We excluded subjects positive for HCV or other types of hepatitis virus, as well as those who had MS when they entered into the cohort (Figure 1). For each subject, demographic characteristics, family history, information about tobacco smoking, alcohol consumption, physical activity, and diet were collected using a questionnaire on 31 December 2011, the day the study was completed. Data from physical examinations and medical histories were collected at entry into the study from hospital records. Subjects were followed until MS (the endpoint) appeared or until study completion. Time of follow-up (in personyears) was calculated for each subject as the difference between the date of entry into the cohort and date of endpoint or date of the end of the study period, whichever came first. All subjects were given a physical examination at the end of the study. Physical examination variables measured were the following: waist circumference measured at the midpoint between the lower border of the rib cage and the iliac crest; seated blood pressure measured 3 times, 1 min apart, using a standard mercury sphygmomanometer, with participants resting for at least 30 minutes before the measurements were made. Blood samples were collected by venipuncture in the morning after 12 hours fasting. Laboratory variables measured from the blood samples were triglycerides (TG), low-density lipoprotein cholesterol
Zhou et al. BMC Public Health 2014, 14:516 http://www.biomedcentral.com/1471-2458/14/516
Page 3 of 6
(LDL-C), HDL-C, TC, fasting plasma glucose (FPG), and hepatitis B serology. Definitions of smoking status for subjects were current smokers (if they were actively smoking) and previous smokers (if they had quit smoking for the past 6 months). Definitions of passive smoking status for subjects reported their history of passive smoking exposure longer than 5 years. Definitions of alcohol consumption status for subjects were current alcohol consumption (if they were actively drinking regardless of amount) and previous smokers (if they had quit drinking for the past 6 months). Definitions of high-energy food intake were subjects who reported that they took fried, smoked, pickled foods and sweets over 5 times in one week. Definitions of fresh fruits and vegetables intake were subjects who reported that they took fruits and fresh vegetables over 5 times in one week. Physical activity was divided into 2 levels, none physical activity was defined as those who exercised less than 1 hour per week.
using Cox proportional hazards models. The covariates in our models included factors that might influence the development of MS. The strength of association was presented as hazards ratio (HR) with 95% confidence intervals (95% CI) and P-values. Analysis was performed using the SAS 9.2 statistical package. All tests were two-sided and p < 0.05 was considered statistically significant. First we carried out crude HR calculation for each potential risk factor adjusting for common confounders such as age, then explored the association between HBV infection and MS by adjusting all potential risk factors.
Definition of metabolic syndrome
Gender
MS was diagnosed based on the updated National Cholesterol Education Program Adult Treatment Panel III criteria [4], requiring the presence of three or more of the following five criteria: (1) waist circumference >90 cm in men or >80 cm in women; (2) TG >150 mg/dL; (3) HDL-C 100 mg/dL or use of oral anti-diabetic agents or insulin. As a retrospective cohort study, all necessary data was tracked and collected in 2012 via database/ medical record. In this type study, we need a good standard to determine disease status at present time though the standard didn’t exist in past, so we selected ATP III as the definition for metabolic syndrome to evaluate the association between metabolic syndrome and hepatitis B infection. Serum viral markers and biochemistry
Blood samples were tested in the laboratory of the Putuo District Hospital. TG, LDL-C, HDL-C, TC and FPG were measured using Shanghai standard laboratory test criteria. HBsAg was detected using routine standard ELISA.
Table 1 Comparison of baseline characteristics between subjects with latent HBV infection (exposed) and the unexposed group Baseline characteristics
Exposed group Unexposed group P-value (N = 480)
(N = 496)
295 (61.5%)
296 (59.7%)
0.5693
RESEARCH ARTICLE
Open Access
Association between hepatitis B virus infection and metabolic syndrome: a retrospective cohort study in Shanghai, China Yanbing Zhou1,2, Yan Cui2, Haiju Deng2 and Jinming Yu3*
Abstract Background: Metabolic syndrome (MS) and hepatitis B (HBV) infection are two major public health problems in China. There are few studies about their association, and the results of these studies are contradictory. We conducted a retrospective cohort study to assess the association between MS and HBV in a Shanghai community-based cohort. Methods: Nine hundred seventy-six Shanghai residents were recruited from the Putuo community. 480 HBV infections were in exposed group and 496 non-infections in unexposed group. All metabolic-related parameters and hepatitis B serology were tested with routine biochemical or immunological methods. “Exposed” was defined by HBV infection represented by hepatitis B surface antigen (HBsAg) and without anti-virus treatment. “Unexposed” were subjects who didn’t infect with HBV (Represented by HBsAg) and no MS when they entered the cohort. MS was defined based on the updated National Cholesterol Education Program Adult Treatment Panel III criteria. The Cox proportional hazards model was used to estimate the hazard ratios (HR) and related 95% confidence intervals (95% CI) for the association between HBV infection and MS over a 20-year follow-up period. Results: Of 976 subjects recruited, 480 had latent HBV infection (exposed subjects). After adjusting for age, the crude HR was 2.46 (95% CI: 1.77, 3.41). After adjusting for potential risk factors of MS (age, gender, smoking, passive smoking, alcohol consumption, physical activity, and diet), the HR was 2.27 (95% CI: 1.52, 3.38). Conclusions: This 20-year follow-up retrospective cohort study in Shanghai showed a positive association between HBV infection and MS.
Background Metabolic syndrome (MS) is a complicated metabolic disorder comprising obesity, hypertension, diabetes, and dyslipidemia. MS has been verified as a risk factor for cardiovascular disease, type 2 diabetes, and renal disease [1-5], and increases mortality from all causes [6]. MS is recognized as a major public health problem worldwide [7,8]. China is endemic for hepatitis B virus (HBV) infection, with a prevalence of nearly 10% [9] in those subjects over 40 in 2006. This age cohort did not receive regular hepatitis B vaccination. Evidence suggests that hepatitis C virus (HCV) infection has an impact on lipid and glucose metabolism [10-14]. A community-based study in Taiwan found HCV infection * Correspondence: [email protected] 3 School of Public Health, Fudan University, Shanghai, P.R. China Full list of author information is available at the end of the article
to be associated with MS (odds ratio 6.4; 95% CI: 1.82 to 22.84) [15]. Similarly to HCV, it is thought that HBV might lead to chronic liver damage by dyslipidemia. A study by Su et al. [16] reported an association between asymptomatic chronic HBV infection and lower serum levels of total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C). This evidence suggests that HBV might affect metabolic profiles and subsequent development of MS. However, studies of the correlation between HBV infection and MS yield contradictory results. Three studies reported a positive association between HBV infection and MS [17-19], two found an inverse association [20,21], and one found no association [22]. The contradictions may be due to small sample size [23] and limitation of subjects to hospital patients [24]. Another study suggested that MS might cause worsening of cirrhosis in chronic HBV patients [25], suggesting a relationship between MS and HBV infection. It is vital to explore the relationship
© 2014 Zhou et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Zhou et al. BMC Public Health 2014, 14:516 http://www.biomedcentral.com/1471-2458/14/516
between two of the major public health problems of China, HBV and MS, to inform prevention and control strategies.
Methods Population and study design
This study was conducted with the approval of the Ethical Review Board in the School of Public Health, Fudan University and conforms to the principles embodied in the Declaration of Helsinki. We evaluated the association between MS and HBV in a community-based retrospective study founded in 1991 in Shanghai. The cohort was from Putuo district, located in the northwest of Shanghai, China. Subjects with HBV were recruited via records from 1991 from the populationbased infectious disease surveillance system. Subjects with latent HBV infections (defined as asymptomatic, but positive for HBV surface antigen for more than 6 months) were classified as “exposed” (Figure 1). After excluding subjects with MS when they entered into the cohort, subjects who had received antiviral or immunosuppressive therapy, and subjects without informed consent, 480 subjects were enrolled into the study. All of them were negative for anti-HCV and other types of hepatitis virus, except for HBV. Four hundred ninety-six subjects negative for HBV surface antigen from the same community were classified
Figure 1 Selection of subjects during study.
Page 2 of 6
as “unexposed”. We excluded subjects positive for HCV or other types of hepatitis virus, as well as those who had MS when they entered into the cohort (Figure 1). For each subject, demographic characteristics, family history, information about tobacco smoking, alcohol consumption, physical activity, and diet were collected using a questionnaire on 31 December 2011, the day the study was completed. Data from physical examinations and medical histories were collected at entry into the study from hospital records. Subjects were followed until MS (the endpoint) appeared or until study completion. Time of follow-up (in personyears) was calculated for each subject as the difference between the date of entry into the cohort and date of endpoint or date of the end of the study period, whichever came first. All subjects were given a physical examination at the end of the study. Physical examination variables measured were the following: waist circumference measured at the midpoint between the lower border of the rib cage and the iliac crest; seated blood pressure measured 3 times, 1 min apart, using a standard mercury sphygmomanometer, with participants resting for at least 30 minutes before the measurements were made. Blood samples were collected by venipuncture in the morning after 12 hours fasting. Laboratory variables measured from the blood samples were triglycerides (TG), low-density lipoprotein cholesterol
Zhou et al. BMC Public Health 2014, 14:516 http://www.biomedcentral.com/1471-2458/14/516
Page 3 of 6
(LDL-C), HDL-C, TC, fasting plasma glucose (FPG), and hepatitis B serology. Definitions of smoking status for subjects were current smokers (if they were actively smoking) and previous smokers (if they had quit smoking for the past 6 months). Definitions of passive smoking status for subjects reported their history of passive smoking exposure longer than 5 years. Definitions of alcohol consumption status for subjects were current alcohol consumption (if they were actively drinking regardless of amount) and previous smokers (if they had quit drinking for the past 6 months). Definitions of high-energy food intake were subjects who reported that they took fried, smoked, pickled foods and sweets over 5 times in one week. Definitions of fresh fruits and vegetables intake were subjects who reported that they took fruits and fresh vegetables over 5 times in one week. Physical activity was divided into 2 levels, none physical activity was defined as those who exercised less than 1 hour per week.
using Cox proportional hazards models. The covariates in our models included factors that might influence the development of MS. The strength of association was presented as hazards ratio (HR) with 95% confidence intervals (95% CI) and P-values. Analysis was performed using the SAS 9.2 statistical package. All tests were two-sided and p < 0.05 was considered statistically significant. First we carried out crude HR calculation for each potential risk factor adjusting for common confounders such as age, then explored the association between HBV infection and MS by adjusting all potential risk factors.
Definition of metabolic syndrome
Gender
MS was diagnosed based on the updated National Cholesterol Education Program Adult Treatment Panel III criteria [4], requiring the presence of three or more of the following five criteria: (1) waist circumference >90 cm in men or >80 cm in women; (2) TG >150 mg/dL; (3) HDL-C 100 mg/dL or use of oral anti-diabetic agents or insulin. As a retrospective cohort study, all necessary data was tracked and collected in 2012 via database/ medical record. In this type study, we need a good standard to determine disease status at present time though the standard didn’t exist in past, so we selected ATP III as the definition for metabolic syndrome to evaluate the association between metabolic syndrome and hepatitis B infection. Serum viral markers and biochemistry
Blood samples were tested in the laboratory of the Putuo District Hospital. TG, LDL-C, HDL-C, TC and FPG were measured using Shanghai standard laboratory test criteria. HBsAg was detected using routine standard ELISA.
Table 1 Comparison of baseline characteristics between subjects with latent HBV infection (exposed) and the unexposed group Baseline characteristics
Exposed group Unexposed group P-value (N = 480)
(N = 496)
295 (61.5%)
296 (59.7%)
0.5693
